The hemodynamic control of pituitary-adrenal function involves neural and humoral mechanisms. Input from atrial and arterial receptors provide the primary neural signal for activation of responses; however, non-hemodynamic neural input from nociceptors and humoral input from the renin-angiotensin system can modulate the pituitary-adrenal response. The interaction between hemodynamic and noxious stimuli will be investigated at selected central neural sites in anesthetized cats. Studies will examine how local chemical stimulation or inhibition of these brain areas affects hormonal release directly and the endocrine response to hemodynamic and nociceptive stimuli presented alone and in combination. Parallel studies will assess effects on the activity of single neurons to determine how the interaction may be encoded within the relevant pathways and will examine effects on local monoaminergic activity in the central nervous system using in vivo voltammetry and push-pull perfusion. The cardiovascular determinants and the relative contributions of the right and left atria in the control of pituitary-adrenal function is still unclear. Atrial volume and filling will be measured with an electrical conductance catheter and related to hormonal responses in chronically-prepared pigs during hemodynamic manipulations that alter these variables. Changes in atrial volume during carotid arterial constriction will also be examined. It is clear that the renin-angiotensin system can affect ACTH release. However, recent studies suggest that angiotensin II may be essential for the response of ACTH to hypovolemia. Studies in dogs will examine the effect of removal of angiotensin II by physiological, pharmacological and surgical techniques, with and without physiological replacement of angiotensin II, on hemorrhage-evoked release of ACTH, cortisol and aldosterone. Plasma ACTH, cortisol, vasopressin, renin, angiotensin II, and aldosterone will be measured by RIA. Adrenal venous and brain perfusates will be assayed for catecholamines by HPLC with electrochemical detection. Adrenal venous steroids will be assayed by HPLC with UV detection. The proposed research will extend the understanding of neural and humoral mechanisms, and their interaction, that mediate the hemodynamic control of pituitary and adrenal function. Accordingly, it may provide new insights concerning the central neural substrate mediating the hormonal responses to hypovolemia and nociception, component sensory inputs that generally accompany traumatic injury.